Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study.
Monitoring EGFR T790M with plasma DNA from lung cancer patients in a prospective observational study.
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DOI：
10.1111/cas.12847
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发表时间：
2016-02
期刊：
影响因子：
5.7
通讯作者：
Hanshin-Saga Collaborative Cancer Study Group
中科院分区：
文献类型：
--
作者：
Sueoka-Aragane N;Katakami N;Satouchi M;Yokota S;Aoe K;Iwanaga K;Otsuka K;Morita S;Kimura S;Negoro S;Hanshin-Saga Collaborative Cancer Study Group
使用血浆DNA检测突变作为液体活检的一种形式已经广泛传播。在半数对EGFR酪氨酸激酶抑制剂（EGFR‐TKI）获得性耐药的肺癌患者中观察到EGFR T790 M。EGFR‐TKI治疗期间通过血浆DNA监测T790 M的有效性尚未确定为重新活检的替代方法。这是一项前瞻性多中心观察性研究，涉及携带EGFR L 858 R或外显子19缺失并接受EGFR‐TKI治疗的非小细胞肺癌患者。主要目的是确定T790 M是否可以使用血浆DNA在疾病进展（PD）患者中检测到。使用突变偏倚PCR和淬灭探针（MBP‐QP）方法检查T790 M，这是我们实验室开发的一种灵敏的全自动系统。从日本的7家医院入组了89例非小细胞肺癌患者。序贯检查显示40%的PD患者血浆DNA中存在T790 M。使用血浆DNA在40%的患者中检测到激活突变，如L 858 R和外显子19缺失，在62%的患者中观察到T790 M或激活突变。分为4个阶段（PD前、PD时、EGFR-TKI停药时和随后），分别在10、19、24和27%的患者中检测到T790 M。吸烟者、男性、外显子19缺失患者和发生新病变的患者证明血浆DNA中T790 M显著频繁存在。使用MBP-QP监测T790 M和血浆DNA反映了接受EGFR-TKI治疗的肺癌患者的临床病程。血浆DNA检测T790 M与EGFR突变类型、外显子19缺失和肿瘤进展相关。仅在14%的PD病例中进行了重新活检，这表明在实践中难以获得重新活检标本。用血浆DNA监测T790 M反映了临床过程，并且在设计后续治疗策略中可能有用。
Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. EGFR T790M has been observed in half of lung cancer patients who have acquired resistance to EGFR tyrosine kinase inhibitors (EGFR‐TKI). Effectiveness of monitoring T790M via plasma DNA during treatment with EGFR‐TKI has not been established as an alternative to re‐biopsy. This was a prospective multicenter observational study involving non‐small cell lung cancer patients carrying EGFR L858R or exon 19 deletions, treated with EGFR‐TKI. The primary objective was to determine whether T790M could be detected using plasma DNA in patients with progressive disease (PD). T790M was examined using the mutation‐biased PCR and quenching probe (MBP‐QP) method, a sensitive, fully‐automated system developed in our laboratory. Eighty‐nine non‐small cell lung cancer patients were enrolled from seven hospitals in Japan. Sequential examinations revealed T790M in plasma DNA among 40% of patients who developed PD. Activating mutations, such as L858R and exon 19 deletions, were detected in 40% of patients using plasma DNA, and either T790M or activating mutations were observed in 62%. Dividing into four periods (before PD, at PD, at discontinuation of EGFR‐TKI and subsequently), T790M was detected in 10, 19, 24 and 27% of patients, respectively. Smokers, males, patients having exon 19 deletions and patients who developed new lesions evidenced significantly frequent presence of T790M in plasma DNA. Monitoring T790M with plasma DNA using MBP‐QP reflects the clinical course of lung cancer patients treated with EGFR‐TKI. Detection of T790M with plasma DNA was correlated with EGFR mutation type, exon 19 deletions and tumor progression. Re‐biopsy could be performed only in 14% of PD cases, suggesting difficulty in obtaining re‐biopsy specimens in practice. Monitoring T790M with plasma DNA reflects the clinical course, and is potentially useful in designing strategies for subsequent treatment.